1. Field of the Invention
The present invention relates to vector-mediated delivery and in vivo expression of polynucleotides encoding proteins that are effective in the treatment of cancer. In particular, the invention relates to the use of recombinant viral and non-viral vectors to deliver genes encoding one or more anti-angiogenic or pro-apoptotic gene products for the treatment of cancer.
2. Background of the Technology
In normal tissue homeostasis is achieved by the balance between the rate of cell proliferation and the rate of cell death. Disruption of this balance is thought to be a major event in the development of cancer. Growth of new blood vessels (angiogenesis) is also known to play a key role in cancer progression in addition to its role in tissue repair. Cellular invasion is an important aspect of cancer metastasis. Currently, standard medical therapies for treatment of cancer including chemotherapy, surgery, radiation therapy and cellular immuno-therapy, have clear limitations with regard to both efficacy and toxicity. To date, these approaches have met with varying degrees of success dependent upon the type of cancer, general health of the patient, stage of disease at the time of diagnosis, etc.
Previous approaches to gene therapy for cancer have focused primarily on the delivery of suicide genes using retroviral, adenoviral and herpes viral vectors. Gene therapy strategies are the subject of ongoing clinical trials, but have not yet demonstrated clinical efficacy. Limited success has been observed, with problems attributed to inefficient gene transfer. Previous anti-cancer strategies include delivery of genes directly to the tumor, direct bolus injection or sustained systemic delivery of anti-cancer agents. Despite advances, lack of significant clinical benefit and/or severe side effects due to the toxicity of currently used treatment regimens remains a problem.
Accordingly, there remains a need for cancer therapies that improve clinical benefit while reducing toxic side effects. Innovative strategies, such as vector-mediated delivery of anti-angiogenic or proapoptotic genes alone or in combination with standard medical treatments, may therefore provide a means for enhanced effectiveness and decreased toxicity in the treatment of cancer.
The present invention addresses this by providing vectors and methods that allow for effective gene delivery and expression of one or more therapeutic genes in patients with cancer. Preferably, such methods exhibit efficient transduction of target cells, good therapeutic yield of the therapeutic factor(s), low toxicity and result in an overall improved clinical benefit for the patient under treatment.